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The eukaryotic polyphosphate (polyP) polymerase VTC complex synthesizes polyP from adenosine triphosphate (ATP) and translocates polyP across the vacuolar membrane to maintain an intracellular phosphate (Pi) homeostasis. To discover how VTC complex solves this fundamental aspect, we determined a cryo-electron microscopy structure of an endogenous VTC complex (Vtc4/Vtc3/Vtc1) fromSaccharomyces cerevisiaeat 3.1 Å resolution. The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3 and three Vtc1 subunits. The transmembrane region forms a polyP selective channel, probably adopting a resting state conformation, in which a latch-like, horizonal helix of Vtc4 limits the entrance. The catalytic Vtc4 central domain locates on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. The SPX domain of Vtc4 positively regulates polyP synthesis and regulation of VTC complex. The non-catalytic Vtc3 regulates VTC through a phoshorylatable loop. Our findings, along with the functional data, allow us to propose a mechanism of polyP channel gating and VTC complex activation.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells. The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P

Background:There is a great controversy about lethal effect of Omicron Variant on vulnerable populations and the measure of full-open or zero community transmission policy. Thus, we designed an observational study to evaluate the outcomes of Omicron-infected patients with pancreatic & biliary cancer (the so-called “King of Cancer”) in order to provide potential evidence for the most appropriate strategy to counter Omicron transmission in Shanghai.Methods: Omicron infected patients with advanced pancreatic & biliary cancer were enrolled from April 15 to May 31, 2022. Four groups were set in this study: Group 1, Omicron-infected cancer patients (N=4); Group 2, non-infected cancer patients (N=4); Group 3, infected non-cancer-afflicted subjects (N=4); Group 4, non-infected non-cancer-afflicted subjects (N=4). On Day 0, 7 and 14 after infection, the blood samples were dynamically collected from all subjects. The primary endpoints were disease severity and survival. Results:By the endpoints in this observational study, Patients No. 2, 3 and 4 died separately at Day 11, 25 and 13 after viral infection, all of whom were patients with advanced cancer, with the death rate up to 75%. Group 1 presented an overall T cell exhaustion status compared with other groups with obviously lower T cell populations and higher B cell% and CD4+T/CD8+T ratio (PConclusions:For patients with advanced pancreatic & biliary cancer, the strict & comprehensive control strategy for COVID-19 epidemic in Shanghai provided a guarantee of low infection and death rate. Conclusively, this policy shall be persisted upon the consideration of the welfare of vulnerable populations.

Objectives To investigate the correlation between brain-derived neurotrophic factor (BDNF) and risk factors, as well as functional outcome in poststroke depression (PSD) or poststroke anxiety (PSA). Design Cohort study. Setting Stroke patients admitted to an urban rehabilitation hospital. Participants Stroke patients (N=162) without any previous history of depression and anxiety. Interventions Not applicable. Main Outcome Measures Sociodemographic information and comorbidities were recorded during hospital admission. Functional outcomes were assessed using FIM scores at time of admission and discharge. The influence of various factors such as BDNF and patient characteristics on functional outcome was investigated. Single-factor effect was examined using simple logistic regression, as was multi-factor effect using multiple logistic regression. The goodness-of-fit of those regression models was evaluated by the integrated area under ROC curve. Results PSD was diagnosed in 61 (37.7%) patients, and PSA was diagnosed in 40 (24.7%). Multiple logistic analysis showed that BDNF, divorce or separation, and history of smoking were significantly associated with the occurrence of PSD but not with the occurrence of PSA. The model combining low BDNF level and divorce or separation improved the prediction for PSD. Among the variables analyzed for prediction of functional outcome, serum BDNF had a minimum correlation with motor FIM scores in PSD but no significant correlation with motor FIM scores in PSA. Conclusions BDNF is a valuable prediction for the occurrence of PSD but not for PSA. More strikingly, ischemic stroke patients who are divorced or separated with low serum BDNF have a much higher risk for PSD. BDNF has a minimum correlation with motor function outcome in PSD but no significant correlation with motor outcome in PSA.

Background and purpose. The identification of a genetic role for cognitive outcome could influence the design of individualized treatment in poststroke rehabilitation. The aim of this study is to determine whether brain-derived neurotrophic factor ( BDNF) Val66Met polymorphism is independently associated with poststroke functional outcome. Methods. A total of 775 stroke patients with genomic data were identified from the Partners HealthCare Biobank, which contains a large number of genotypes from Biobank’s consented patients. Of 775 stroke patients who met the inclusion/exclusion criteria, 86 were enrolled. Functional outcomes were assessed using the Functional Independence Measure scores at the time of admission and discharge. Logistic and linear regression models adjusted for covariate variables, including age, sex, and medical conditions, were used to evaluate the association between BDNF Val66Met and functional outcome. Results. We detected a significant correlation between Met alleles and lower cognitive function at discharge in both ischemic and hemorrhagic stroke patients. Genotyping findings confirmed that BDNF Met allele frequency was higher in contrast to Val/Val allele frequency in lower cognitive functional recovery. Furthermore, after adjusting for covariate variables, BDNF Met alleles were found to be associated with lower cognitive outcome [ P = .003; odds ratio (OR) = 5.95 (1.81-19.52)] and recovery [ P = .006; OR = 3.16 (1.4-7.15)], especially with lower problem solving, expression, and social recovery in all stroke patients. Conclusions. Met allele carriers exhibited impaired poststroke cognitive function. The BDNF genotype may be a useful predictor of cognitive function in inpatient poststroke rehabilitation.

The urban green space ratio (GSR) is the ratio of the urban greening land area to the built-up area and is an indicator for controlling land use for greening in urban development in China....

Supplemental material, Supplemental_Material_10.15_cleancopy for BDNF Met allele Is Associated With Lower Cognitive Function in Poststroke Rehabilitation by Zhenxiang Han, Lili Qi, Qinfeng Xu, Mingzhu Xu, Lei Cai, John Wong, Xinjia Hu, Xun Luo, Jiening Wang, Yuling Zhang, Yapeng Li and Qing Mei Wang in Neurorehabilitation and Neural Repair

BackgroundLiver cancer is the second leading causes of cancer-related death globally. Pyrroline-5-carboxylate reductase 1 (PYCR1) plays a critical role in metabolic profiles of tumors. Therefore, it is necessary to explore the mechanisms of PYCR1 on cell growth and survival in hepatocellular carcinoma (HCC).MethodsProtein and mRNA expression levels of PYCR1 in 140 pairs of tumor and adjacent normal liver tissues of HCC patients were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Expressions of PYCR1 were inhibited in BEL-7404 cells and SMMC-7721 cells using gene interference technology. The cell proliferation was detected by Celigo and MTT assay. The colony formation assay was also performed. The cell apoptosis was measured by flow cytometric assay. The effect of PYCR1 interference on tumor growth was observed by xenograft nude mice assay in vivo. The downstream pathway of PYCR1 interference was searched by microarray and bioinformatics analysis, and validated by qRT-PCR and western blot.ResultsPYCR1 levels were significantly up-regulated in HCC tumor tissues than adjacent normal liver tissues in both protein and mRNA levels (P P P P P ConclusionPYCR1 interference could inhibit cell proliferation and promote cell apoptosis in HCC through regluting JNK/IRS1 pathway. Our study will provide a drug target for HCC therapy and a potential biomarker for its diagnosis or prognosis.

// Wei Xia 1, * , Juhua Zhuang 1, * , Guoyu Wang 1 , Jing Ni 1 , Jiening Wang 2 , Ying Ye 1 1 Department of Nuclear Medicine, Seventh People’s Hospital of Shanghai University of TCM, Shanghai, China 2 Department of Integrated TCM & western medcine, President’s Office of Seventh People’s Hospital of Shanghai University of TCM, Shanghai, China * These authors have contributed equally to this work and should be considered as co-first authors Correspondence to: Jiening Wang, email: doctorwjn@126.com Ying Ye, email: doctoryeying@126.com Keywords: P4HB, GRP78, hepatocellular carcinoma, tumorigenesis, epithelial-to-mesenchymal transition Received: July 25, 2016 Accepted: December 01, 2016 Published: December 28, 2016 ABSTRACT P4HB and GRP78 are molecular chaperones involved in cellular response to ER stress. They have been linked to cancer progression; however, their roles in hepatocellular carcinoma (HCC) are largely unclear. In this study, we found that P4HB is overexpressed in human HCC tissues and cell lines. Higher tumoral P4HB levels are correlated with more advanced disease and poorer survival. GRP78 expression is inversely correlated with P4HB in human HCC tissues, and downregulated by P4HB in HCC cell lines. P4HB overexpression promotes HCC cell growth, migration, invasion and epithelial-to-mesenchymal transition (EMT) in vitro . GRP78 overexpression not only inhibits HCC cell growth, migration, invasion and EMT, but also antagonizes the oncogenic effects of P4HB overexpression. Furthermore, P4HB silencing inhibits HCC tumorigenesis in vivo . Taken together, our results provided evidence that P4HB promotes HCC progression through downregulation of GRP78 and subsequent upregulation of EMT.

The aim of the present study was to investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) in the chemoresistance of liver cancer. Drug-resistant liver cancer cell lines, such as HepG2/adriamycin (ADR) cells, were treated and screened using adriamycin. Gene interference was used to silence the expression of P4HB in liver cancer cells. Cell viability, invasiveness and migration were assessed using CCK8, Transwell and wound healing assays, respectively. In addition, changes to key genes and proteins in the epithelial-mesenchymal transition (EMT) and β-catenin/Snail pathway were analyzed using reverse transcription-quantitative PCR and western blotting. Drug-resistant HepG2/ADR cells were successfully cultivated; the IC50 to ADR for HepG2/ADR and HepG2 cell lines was 4.85 and 0.61 µM, respectively. HepG2/ADR cells exhibited higher invasion and migration abilities compared with HepG2 cells (P

Colon cancer is the second most lethal malignancy worldwide. A better understanding of colon cancer at the molecular level may increase overall survival rates. Previous studies have indicated that prolyl 4‑hydroxylase, β polypeptide (P4HB) is associated with tumorigenesis in colon cancer; however, its role and molecular mechanisms in colon cancer remain unclear. In the present study, the cellular responses to P4HB in human colon cancer cell lines were investigated by proliferation and apoptosis assays, western blotting, and immunohistochemistry. The results showed that expression of P4HB was higher in colon cancer tissues compared within adjacent normal tissues. P4HB knockdown increased the apoptosis of human HT29 cells. Furthermore, P4HB knockdown reduced the activation of signal transducer and activator of transcription 3 (STAT3) and promoted accumulation of reactive oxygen species (ROS). Inhibiting the accumulation of ROS abrogated the increased cell apoptosis induced by P4HB knockdown. Notably, decreased ROS levels effectively antagonized the effects of P4HB on STAT3 inactivation. In conclusion, these findings suggested that P4HB knockdown may induce HT29 human colon cancer cell apoptosis through the generation of ROS and inactivation of the STAT3 signaling pathway.

AKAP12/Gravin (A kinase anchor protein 12) belongs to the group of A-kinase scaffold proteins and functions as a tumor suppressor in some human primary cancers. While AKAP12 is found consistently downregulated in hepatocellular carcinoma (HCC), its involvement in hepatocarcinogenesis has not been fully elucidated. We identified targeting sites for miR-103 in the 3'-untranslated region (3'-UTR) of AKAP12 by bioinformatic analysis and confirm their function by a luciferase reporter gene assay. We reveal miR-103 expression to be inversely correlated with AKAP12 in HCC tissue samples and show that overexpressed miR-103 promotes cell proliferation and inhibits apoptosis by downregulating AKAP12 expression in HCC cell lines. On the other hand, repression of miR-103 suppresses proliferation and promotes apoptosis in HCC cells by increasing AKAP12. In xenografted HCC tumors, overexpression of AKAP12 suppresses tumor growth whereas overexpression of miR-103 enhances tumor growth while repressing AKAP12. Since the activation of telomerase is crucial for cells to gain immortality and proliferation ability, we investigated whether AKAP12 expression affected telomerase activity in HCC cells. Both AKAP12 overexpression and protein kinase Cα (PKCα) inhibition prevent nuclear translocation and phosphorylation of TERT and reduce telomerase activity in HCC cells. These findings indicate that miR-103 potentially acts as an oncogene in HCC by inhibiting AKAP12 expression and raise the possibility that miR-103 increases telomerase activity by increasing PKCα activity. Thus, miR-103 may represent a new potential diagnostic and therapeutic target for HCC treatment.

Hepatocellular carcinoma (HCC) is a common malignancy associated with a high risk of recurrence and metastasis and a poor prognosis. Here, we examined the involvement of the pseudokinase Tribbles 1 (TRIB1), a scaffold protein associated with several malignancies, in HCC and investigated the underlying mechanisms. TRIB1 was upregulated in HCC tissues and cell lines in correlation with low levels of p53. TRIB1 gain and loss of function experiments indicated that TRIB1 promoted HCC cell viability concomitant with the downregulation of p53, and induced HCC cell migration, invasion, and epithelial-mesenchymal transition. TRIB1 was identified as a target of microRNA-23a (miR-23a), and miR-23a overexpression downregulated TRIB1 and upregulated p53 in HCC cells. Ectopic expression of TRIB1 upregulated β-catenin and its effectors c-myc and MMP-7 in a p53-dependent manner. TRIB1 silencing inhibited tumor growth and promoted apoptosis in vivo via a mechanism that would involve the modulation of p53 and β-catenin signaling. The present results indicate that TRIB1 promotes HCC tumorigenesis and invasiveness via a feedback loop that involves the modulation of its expression by miR-23a with the likely downregulation of p53, and suggest the involvement of the β-catenin signaling pathway. These findings suggest potential targets for the treatment of HCC and therefore merit further investigation.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second-most frequent cause of cancer-associated deaths worldwide. Previously, increasing studies report that microRNAs (miRNAs/miRs) are abnormally expressed in various types of human cancers and may participate in the tumourigenesis and tumour development of HCC. miRNA-based targeted therapy is effective against different molecular targets and may increase the sensitisation of cancer cells to therapy by several folds. Therefore, further validation of potentially important miRNAs involved in HCC initiation and progression may provide valuable insights into the treatment of patients with HCC. miR-495 is abnormally expressed in multiple types of human cancers. However, the expression level and roles of miR-495 in HCC have yet to be completely elucidated. In the present study, miR-495 expression was frequently downregulated in HCC tissues and cell lines, and miR-495 expression levels were significantly correlated with tumour size, tumor-node-metastasis (TNM) stage and lymph node metastasis in patients with HCC. Functional assays revealed that miR-495 overexpression inhibited cell proliferation and invasion in HCC. Insulin-like growth factor receptor-1 (IGF1R) was identified as a direct target gene of miR-495 in HCC. IGF1R was upregulated in HCC tissues and negatively correlated with miR-495 expression level. The upregulation of IGF1R rescued the miR-495-induced tumour-suppressive roles in HCC cell proliferation and invasion, and the restored miR-495 expression inactivated the protein kinase B and extracellular regulated protein kinase signalling pathways in HCC. These results provide novel insights into the molecular mechanism underlying HCC progression, and suggest that miR-495 may be investigated as a novel therapeutic target for patients with this disease.

Lung cancer is the most common cause of cancer- associated mortality for men and women worldwide. An increasing number of studies have reported that the abnormal expression of microRNAs contributes to the pathogenesis of the majority of human cancer types, including non-small cell lung cancer (NSCLC). The present study aimed to measure microRNA-650 (miR-650) expression in NSCLC and evaluate its function in NSCLC cells. Reverse transcription-quantitative polymerase chain reaction was used to determine miR-650 expression in NSCLC tissue samples and cell lines. Assays for cell proliferation, migration and invasion were performed to investigate the roles of miR-650 on NSCLC progression. Furthermore, the mechanisms underlying the effects of miR-650 on NSCLC cell growth and metastasis were determined. In the current study, miR-650 was demonstrated to be highly expressed in NSCLC tissue samples and cell lines. Inhibition of expression of miR-650 suppressed NSCLC cell proliferation, migration and invasion in vitro. Additionally, large tumor suppressor kinase 2 (LATS2) was identified as a direct target gene of miR-650 in NSCLC. LATS2 was revealed to be significantly downregulated in NSCLC tissues and was negatively correlated with miR-650 expression. Notably, LATS2 re-expression decreased NSCLC cell proliferation, migration and invasion; similar to the effects induced by miR-650 underexpression. In conclusion, the results of the current study suggest that miR-650 may serve as an oncogene by direct targeting LATS2 in NSCLC formation and progression.

Introduction/Background The Val66Met single nucleotide polymorphism (SNP rs6265) of the Brain-Derived Neurotrophic Factor (BDNF) gene decreases BDNF secretion. Previous studies in patients with stroke have shown that the Val66Met polymorphism is associated with poorer outcome. The aim of this study was to determine whether or not the BDNF Val66Met genotype is associated with functional outcome after stroke in our inpatient rehabilitation sample. Material and method One hundred and five individuals admitted for inpatient rehabilitation following a stroke and who were also enrolled in the Partners HealthCare Biobank. The genotypes for BDNF SNP rs6265 for individuals with stroke were obtained from the Partners HealthCare Biobank Portal. Main outcome measures were the Functional Independence Measure (FIM) on admission and discharge. Stroke outcome was defined as the change in FIM scores between discharge and admission. The prediction of motor and cognitive outcome at discharge was modeled using BDNF Val66Met genotype. Regression analyses were performed to identify the significant associations of the genetic factor with functional outcome. Results Individuals with stroke who were homozygous for the GG genotype had significantly lower FIM cognition subscale (P = 0.023) and memory subscores (P = 0.011) as compared to those with either the heterozygous AG or homozygouse AA genotypes. In addition, the GG genotype was a significant predictor for poor memory outcome (P = 0.021, OR = −0.036 [B = −0.067 to −0.005]) when controlling for age and gender. This association may be due to the association with memory since the memory score is contained within the cognition subscale. Conclusion The preliminary data suggests that BDNF Val66Met polymorphsim may impede stroke recovery, especially cognitive function. Further studies with larger samples are warranted to elucidate the role and mechanism of BDNF genetic variants in stroke recovery.

U-turn maneuver is a special taxiing behavior on the ground. This paper studied the behavior and aimed to research the problem of position and attitude during the movement. From the perspective of airport tower control simulation, the calculation methods that the aircraft did U-turn maneuver under the nonholonomic constraints were proposed. According to the real geometrical constraints and kinematic equations, a method, suitable for simulation, deduction and calculation, was designed. At last, with the help of MATLAB, the validity of this method was confirmed. Compared with dynamics model, this method was easy to be computed and more suitable for the application to scene driven. This paper, moreover, designed the structural frame of 3D scene driven for the tower control simulation. DOI : http://dx.doi.org/10.11591/telkomnika.v12i3.4495 Full Text: PDF

A sort-last parallel volume Splatting algorithm based on commodity PC clusters, which integrates hybrid data-space and image-space partitioning schemes, is proposed in this paper. Under the sort-last strategy, sorting is deferred until the end of the rendering pipeline. The approach also adopts a divide-and-conquer strategy and an object-order data decomposition scheme to distribute the volume among nodes in the PC clusters. The proposed method has excellent features including high scalability, predictable communication patterns and load balance in the rendering of large scale volume data sets on commercial PC clusters which have no high-end graphics adaptors equipped.

In computer graphics, silhouette extracting and rendering has an important role in a number of application. Special features such as silhouette and crease of a polygonal scene are usually displayed by identifying for the corresponding geometry especially in non-photorealistic rendering (NPR). We present an algorithm for extracting and rendering silhouette outlines and crease edges of 3D polygonal meshes in image space. This algorithm is simple and suitable for modern programmable graphics hardware implementation. It can generate NPR image synthesis in real-time. Our experimental results show it satisfies real-time interactive needs.

In this paper we describe an approach to the procedural techniques of pattern generation to be used in rendering, based on genetic algorithms. Procedural textures exhibit many advantages over traditional surface texturing techniques, but unfortunately it is difficult for us to find the correct procedural texture and appropriate parameters to create the desired texture can be a daunting task for even the most experienced user. Upon analysis of genetic programming techniques and image matching evaluation scheme, we attempt to generate procedural 3D cloud texture automatically.

In this paper, Distributed Virtual Reality (DVR) technology applied in Electronical Commerce (EC) is discussed. DVR has the capability of providing a new means for human being to recognize, analyze and resolve the large scale, complex problems, which makes it develop quickly in EC fields. The technology of CSCW (Computer Supported Cooperative Work) and middleware is introduced into the development of EC-DVR system to meet the need of a platform which can provide the necessary cooperation and communication services to avoid developing the basic module repeatedly. Finally, the paper gives .a platform structure of EC-DVR system.

It would be more convinced if we can provide more realistic visual effects in a VR system. Bump mapping can simulate a surface bumpy appearance without any overload of increasing extra polygons. Techniques of programmable per-vertex shader and per-pixel shader have been introduced in recent years based on newly developed graphics hardware armed with powerful GPU. This makes ease in realizing real-time bump mapping and complex lighting computation. Firstly, the mathematics of bump mapping is discussed. And then real-time bump mapping implementation using per-pixel shading supported by programmable hardware is described. Finally we present our experimental result. It shows our method is desirable.

The computer aided 3D display system, flicker-free field sequential stereoscopic image display system, is newly developed. This system is composed of personal computer, liquid crystal glasses driving card, stereoscopic display software and liquid crystal glasses. It can display field sequential stereoscopic images at refresh rate of 70 Hz to 120 Hz. A typical application of this system, 3D vision test system, is mainly discussed in this paper. This stereoscopic vision test system can test stereoscopic acuity, cross disparity, uncross disparity and dynamic stereoscopic vision quantitatively. We have taken the use of random-dot- stereograms as stereoscopic vision test charts. Through practical test experiment between Anaglyph Stereoscopic Vision Test Charts and this stereoscopic vision test system, the statistical figures and test result is given out.